Skip to main content
Log in

Irinotecan and nedaplatin as salvage therapy for patients with advanced germ cell tumors following intensive treatment with cisplatin-based combination chemotherapies

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

To analyze the clinical outcomes of the irinotecan plus nedaplatin (IN) regimen in patients with advanced germ cell tumors (GCTs) refractory to cisplatin-based combination chemotherapies.

Methods

This study included a total of 20 consecutive advanced GCT patients who were categorized into intermediate- or poor-risk GCT groups according to the International Germ Cell Consensus Classification, and were judged to show refractory or relapsed disease after bleomycin, etoposide and cisplatin and cisplatin, ifosfamide and paclitaxel therapies. All 20 patients subsequently received IN therapy (irinotecan 100 mg/m2 on days 1 and 15; nedaplatin 100 mg/m2 on day 1) every 4 weeks.

Results

Following a median of 3 cycles of IN, 9 patients (45 %) achieved normalization of serum tumor markers. In addition, surgical resection of the residual tumors following IN was performed in 5 patients, of whom 4 were pathologically diagnosed with no viable cancer cells. At a median follow-up of 9 months, 11 patients (55 %) were alive, including 7 (35 %) with no evidence of disease, whereas the remaining 9 (45 %) died of disease progression. The median duration of overall survival after the introduction of IN to these 20 patients was 13.4 months. Severe hematological toxicities were observed in all patients, but were manageable. Although fatal treatment-related interstitial pneumonia occurred in 1 patient, other non-hematological toxicities were generally tolerable.

Conclusions

Considering the markedly unfavorable characteristics of the included patients with advanced GCT who were intensively treated with cisplatin-based combination chemotherapies, IN could be regarded as having promising therapeutic activity with an acceptable toxicity profile.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Purdue MP, Devesa SS, Sigurdson AJ et al (2005) International patterns and trends in testis cancer incidence. Int J Cancer 115:822–827

    Article  CAS  PubMed  Google Scholar 

  2. Nakamura T, Miki T (2010) Recent strategy for the management of advanced testicular cancer. Int J Urol 17:148–157

    Article  PubMed  Google Scholar 

  3. Nichols CR, Roth BJ, Loehrer PJ et al (1994) Salvage chemotherapy for recurrent germ cell cancer. Semin Oncol 5:102–108

    Google Scholar 

  4. Porcu P, Bhatia S, Einhorn LH (2000) Results of treatment after relapse from high-dose chemotherapy in germ cell tumors. J Clin Oncol 18:1181–1186

    CAS  PubMed  Google Scholar 

  5. Mathijssen RH, Loos WJ, Verweij J (2002) Pharmacology of topoisomerase I inhibitors irinotecan (CPT-11) and topotecan. Curr Cancer Drug Targets 2:103–123

    Article  CAS  PubMed  Google Scholar 

  6. Xu Y, Villalona-Calero MA (2002) Irinotecan: mechanisms of tumor resistance and novel strategies for modulating its activity. Ann Oncol 13:1841–1851

    Article  CAS  PubMed  Google Scholar 

  7. Kollmannsberger C, Rick O, Klaproth H et al (2002) Irinotecan in patients with relapsed or cisplatin-refractory germ cell cancer: a phase II study of the German Testicular Cancer Study Group. Br J Cancer 87:729–732

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Pectasides D, Pectasides M, Farmakis D et al (2004) Oxaliplatin and irinotecan plus granulocyte-colony stimulating factor as third-line treatment in relapsed or cisplatin-refractory germ-cell tumor patients: a phase II study. Eur Urol 46:216–221

    Article  CAS  PubMed  Google Scholar 

  9. Miki T, Sawada M, Nonomura N et al (1997) Antitumor effect of CPT-11, a camptothecin derivative, on human testicular tumor xenografts in nude mice. Eur Urol 31:92–96

    CAS  PubMed  Google Scholar 

  10. Akaza H, Togashi M, Nishio Y et al (1992) Phase II study of cisdiammine(glycolato)platinum, 254-S, in patients with advanced germ-cell testicular cancer, prostatic cancer, and transitional-cell carcinoma of the urinary tract. 254-S Urological Cancer Study Group. Cancer Chemother Pharmacol 31:187–192

    Article  CAS  PubMed  Google Scholar 

  11. International Germ Cell Cancer Collaborative Group (1997) International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol 15:594–603

    Google Scholar 

  12. Kumano M, Miyake H, Hara I et al (2007) First-line high-dose chemotherapy combined with peripheral blood stem cell transplantation for patients with advanced extragonadal germ cell tumors. Int J Urol 14:336–338

    Article  CAS  PubMed  Google Scholar 

  13. Nishikawa M, Miyake H, Muramaki M et al (2014) Efficacy and tolerability of TIP (paclitaxel, ifosfamide and cisplatin) incorporated into induction chemotherapy for patients with intermediate- or poor-risk metastatic germ cell tumors. Med Oncol 31:296

    Article  PubMed  Google Scholar 

  14. Farhat F, Culine S, Théodore C et al (1996) Cisplatin and ifosfamide with either vinblastine or etoposide as salvage therapy for refractory or relapsing germ cell tumor patients: the Institut Gustave Roussy experience. Cancer 77:1193–1197

    Article  CAS  PubMed  Google Scholar 

  15. Pico JL, Rosti G, Kramar A et al (2005) European Group for Blood and Marrow Transplantation (EBMT). A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours. Ann Oncol 16:1152–1159

    Article  PubMed  Google Scholar 

  16. Motzer RJ, Sheinfeld J, Mazumdar M et al (2000) Paclitaxel, ifosfamide, and cisplatin second-line therapy for patients with relapsed testicular germ cell cancer. J Clin Oncol 18:2413–2418

    CAS  PubMed  Google Scholar 

  17. Mead GM, Cullen MH, Huddart R et al (2005) A phase II trial of TIP (paclitaxel, ifosfamide and cisplatin) given as second-line (post-BEP) salvage chemotherapy for patients with metastatic germ cell cancer: a medical research council trial. Br J Cancer 93:178–184

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Miki T, Sawada M, Nonomura N et al (1997) Antitumor effect of CPT-11, a camptothecin derivative, on human testicular tumor xenografts in nude mice. Eur Urol 31:92–96

    CAS  PubMed  Google Scholar 

  19. Kanzawa F, Koizumi F, Koh Y et al (2001) In vitro synergistic interactions between the cisplatin analogue nedaplatin and the DNA topoisomerase I inhibitor irinotecan and the mechanism of this interaction. Clin Cancer Res 7:202–209

    CAS  PubMed  Google Scholar 

  20. Nicolai N, Necchi A, Gianni L et al (2009) Long-term results of a combination of paclitaxel, cisplatin and gemcitabine for salvage therapy in male germ-cell tumours. BJU Int 104:340–346

    Article  CAS  PubMed  Google Scholar 

  21. Nakamura T, Ueda T, Oishi M et al (2015) Salvage combined chemotherapy with paclitaxel, ifosfamide and nedaplatin for patients with advanced germ cell tumors. Int J Urol 22:288–293

    Article  CAS  PubMed  Google Scholar 

  22. Yamada S, Saito H, Ohara S et al (2013) Salvage chemotherapy with docetaxel, ifosfamide and nedaplatin (DIN) for patients with advanced germ cell tumors: a preliminary report. Jpn J Clin Oncol 43:734–739

    Article  PubMed  Google Scholar 

  23. Rothenberg ML, Eckardt JR, Kuhn JG et al (1996) Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer. J Clin Oncol 14:1128–1135

    CAS  PubMed  Google Scholar 

  24. Pitot HC, Wender DB, O’Connell MJ et al (1997) Phase II trial of irinotecan in patients with metastatic colorectal carcinoma. J Clin Oncol 15:2910–2919

    CAS  PubMed  Google Scholar 

Download references

Conflict of interest

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hideaki Miyake.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nishikawa, M., Miyake, H. & Fujisawa, M. Irinotecan and nedaplatin as salvage therapy for patients with advanced germ cell tumors following intensive treatment with cisplatin-based combination chemotherapies . Int J Clin Oncol 21, 162–167 (2016). https://doi.org/10.1007/s10147-015-0861-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-015-0861-0

Keywords

Navigation